The overall objective is to contribute to a better understanding of the hormonal regulation of calcium homeostasis as a rational basis for the prevention and medical management of calcium-related diseases, especially those occurring in old age. Project 1. To determine the factors responsible for and the mechanisms involved in the C-cell hyperplasia and increased thyroidal and serum calcitonin (CT) that we discovered are associated with goiters produced in rats by a low-iodine diet or propylthiouracil. Specifically, what is the role of TSH (and/or TSH (and/or TRF, PTH and other factors? Project 2. To document further the relationship between age, C-cell proliferation, and increased CT in rats. To determine at what age or ages substantial changes occur in C-cells and CT in rats. To determine the factors and mechanisms involved in these changes. To evaluate physiological and pathophysiological effects of these changes. To extend these studies to the thyroid "dark cells". Project 3. To investigate further the protective effect of endogenous or injected CT against calcification of the kidney and cardiovascular system, which can be induced readily by parathyroid hormone or vitamin D and the possible role of CT in the prevention of metastatic calcification associated with tertiary hyperparathyroidism. To facilitate this study a rat model in which C-cells have been removed and follicular function retained (partial thyroidectomy leaving isthus only) will be used. Development of a second rat model with tertiary hyperparathyroidism will also be attempted.